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BY BY MAGDY ABDELRAHMAN MOHAMEDMAGDY ABDELRAHMAN MOHAMED
20122012
AMENORRHEAAMENORRHEA
Primary Amenorrhea
is defined either as absence of menses by age 14 years with no development of secondary sexual characteristics OR as absence of menses by age 16 years with normal development of secondary sexual characteristics.
Secondary amenorrhea
is defined as the cessation of menstruation for at least 6 months or for at least 3 of the previous 3 cycle intervals
Thelarche (breast development)Thelarche (breast development)– Requires estrogenRequires estrogenPubarche/adrenarche (pubic hair development)Pubarche/adrenarche (pubic hair development)– Requires androgensRequires androgens
MenarcheMenarcheRequires:Requires:– GnRH from the hypothalamusGnRH from the hypothalamus– FSH and LH from the pituitaryFSH and LH from the pituitary– Estrogen and progesterone from the ovariesEstrogen and progesterone from the ovaries– Normal outflow tractNormal outflow tract
Events of PubertyEvents of Puberty
Magnitude of the problem Secondary amenorrhea (prevalence about 3%) Primary amenorrhea (prevalence about 0.3%) Between 10 and 20% of women complaining of
infertility have amenorrhea . Up to 50% of competitive runners (training 80 miles
per week) and up to 44% of ballet dancers have amenorrhea.
ETIOLOGY OF ETIOLOGY OF PRIMARY AMENORRHEA
Secondary sexual characteristics present
Constitutional delay Genito-urinary malformation, e.g. imperforate hymen,
transverse vaginal septum, absent vagina with or without a functioning uterus
Androgen insensitivity Resistant ovary syndrome Pregnancy
Secondary sexual characteristics absent
Hypothalamic dysfunction, e.g. chronic illness, anorexia nervosa, weight loss, 'stress'
Gonadotrophin deficiency, e.g. Kallman's syndrome Hypopituitarism Hyperprolactinemia Hypothyroidism Gonadal failure, e.g. ovarian dysgenesis/agenesis,
premature ovarian failure
Ambiguous external genitalia
Congenital adrenal hyperplasia Androgen-secreting tumor 5-Alpha-reductase deficiency
CAHCAH
Sertoli-Leydig Cell TumorSertoli-Leydig Cell Tumor
Turner's syndrome Turner's syndrome is
caused by either a complete absence or a partial abnormality of one of the two X chromosomes. About 50% have mosaic forms such as 45X/46XX or 45X/46XY
Features : short stature, web neck, lymphedema, shield chest with widely spaced nipples, wide carrying angle, coarctation of the aorta, and streak ovaries
Uterovaginal agenesisUterovaginal agenesis
15% of primary amenorrhea 15% of primary amenorrhea Normal secondary development & external Normal secondary development & external female genitaliafemale genitaliaNormal female range testosterone levelNormal female range testosterone level
Absent uterus and upper vagina & normal Absent uterus and upper vagina & normal ovariesovariesKaryotype 46-XXKaryotype 46-XX1515--30% associated renal, skeletal and middle 30% associated renal, skeletal and middle ear anomaliesear anomalies
Androgen insensitivity syndrome (AIS)
Formerly known as testicular feminization, 46XYFailure of normal masculinization of the external genitalia in chromosomally male individuals. This failure of virilization can be either complete (CAIS) or partial (PAIS), depending on the amount of residual receptor functionAffected individuals have normal testes with normal production of testosterone and normal conversion to dihydrotestosterone (DHT), which differentiates this condition from 5-alpha reductase deficiency
Imperforate hymenImperforate hymen represents the most common and most distal form of vaginal outflow obstructionClinical presentations range from an incidental finding on physical examination of an asymptomatic patient to discovery on an evaluation for primary amenorrhea or abdominal or back painThe differential diagnosis of uterovaginal obstruction includes disorders of vaginal development, such as transverse vaginal septum or complete vaginal agenesis.
Imperforate hymen
Constitutional delay
In this condition there is no anatomical abnormality and endocrine investigations show normal results
It is caused by immature pulsatile release of gonadotrophin-releasing hormone; maturation eventually occurs spontaneously
ASSESSMENT OF ASSESSMENT OF PRIMARY AMENORRHEAPRIMARY AMENORRHEA
TSH elevatedhypothyroidism
Normal
bone age delayed
constitutional delayNormal
LH, FSH, and prolactin levels
elevated
karyotype.
low or within
reference range
head MRI
45,XO, the cause is gonadal dysgenesis
46,XX, the primary cause is ovarian failure
•pituitary tumor or a brain lesion
•drug use, an eating disorder, athleticism, or psychosocial stress
If puberty delayed
TSH and prolactin levels
progestin challenge
within reference range
consider anovulatory cycles
PCO
E2/progestin challenge
outlet obstruction obtain FSH and LH levels.
low or within reference range
head MRI
exclude chronic disease, anorexia nervosa, or psychosocial stress
high
karyotype
Turner syndkaryotype is normal (46,XX),
the cause is ovarian failure
elevatedhypothyroidism and
hyperprolactinemia
+VE-VE
If puberty not delayed
+-
genital tract abnormalities karyotype
If the karyotype is 46,XY If the karyotype is 46,XX
testosterone levels
male range female range
androgen insensitivity testicular regression
or gonadal enzyme deficiency.
müllerian agenesis (ie, Rokitansky-Kuster-Hauser
syndrome).
Breast development, pubertal growth spurt, and adrenarche are delayed or absent
in persons with
hypothalamic pituitary failure
adrenarche occurs normally, while estrogen-dependent breast development and the
pubertal growth spurt are absent or delayed
isolated ovarian insufficiency or failure
Etiology of Etiology of secondary amenorrhea
No features of androgen excess present
Physiologic, e.g. pregnancy, lactation, menopause Iatrogenic, e.g. depot medroxyprogesterone acetate
contraceptive injection, radiotherapy, chemotherapy Systemic disease, e.g. chronic illness, hypo- or
hyperthyroidism Uterine causes, e.g. cervical stenosis, Asherman's
syndrome (intra-uterine adhesions)
Ovarian causes, e.g. premature ovarian failure, resistant ovary syndrome
Hypothalamic causes, e.g. weight loss, exercise, psychological distress, chronic illness, idiopathic
Pituitary causes, e.g. hyperprolactinaemia, hypopituitarism, Sheehan's syndrome
Features of androgen excess present
Polycystic ovary syndrome Cushing's syndrome Late-onset congenital adrenal hyperplasia Adrenal or ovarian androgen-producing tumor
Polycystic ovary syndrome
This condition is characterized by hirsutism, acne, alopecia, infertility, obesity, and menstrual abnormalities (amenorrhea in 19% of cases)
Ultrasound examination of the ovaries typically shows multiple, small peripheral cysts. up to a third of women in the general population have polycystic ovaries on ultrasound examination .
Endocrine abnormalities include increased serum concentrations of testosterone, prolactin, luteinizing hormone (LH) (with normal follicle-stimulating hormone [FSH] levels), and insulin resistance with compensatory hyperinsulinemia
Asherman’s SyndromeAsherman’s Syndrome
Menopause/ovarian failure occurring before the age of 40 years is considered premature
Auto-immune disease is the most common cause; auto-antibodies to ovarian cells, gonadotrophin receptors, and oocytes have been reported in 80% of cases
Before puberty or in adolescents, ovarian failure is usually due to a chromosomal abnormality, e.g. Turner mosaic, or previous radiotherapy, or chemotherapy
Premature ovarian failure
Ovarian failure (premature menopause)
chromosomal anomalies
autoimmune disease
If the woman is under 30, a karyotype should be
performed to rule out any mosaicism involving a Y
chromosome
It is necessary to screen for thyroid, parathyroid, and adrenal
dysfunction
If a Y chromosome is found the gonads should be surgically excised
Autoimmune related dysfunction The most common association is with thyroid The most common association is with thyroid disease, but the parathyroids and adrenals can disease, but the parathyroids and adrenals can also be affectedalso be affectedSeveral studies have shown laboratory evidence of Several studies have shown laboratory evidence of immune problems in about 15-40% of women with immune problems in about 15-40% of women with premature ovarian failurepremature ovarian failureIn general, ovarian biopsy is not indicated in In general, ovarian biopsy is not indicated in patients with premature ovarian failure since no patients with premature ovarian failure since no clinically useful information will be obtainedclinically useful information will be obtained
Hyperprolactinemia A prolactinoma is the commonest cause of
hyperprolactinemia (60% of cases) Other causes include non-functioning pituitary adenoma
(disrupting the inhibitory influence of dopamine on prolactin secretion)
dopaminergic antagonist drugs (e.g. phenothiazines, haloperidol, clozapine, methyldopa, cimetidine); primary hypothyroidism (thyrotrophin-releasing hormone stimulates the secretion of prolactin), or it may be idiopathic
Prolactin acts directly on the hypothalamus to reduce the amplitude and frequency of pulses of gonadotrophin-releasing hormone
Weight-related amenorrhoea
A regular menstrual cycle is unlikely to occur if the body mass index (BMI) is less than 19 (normal range 20-25)
Weight loss may be due to illness, exercise, or eating disorders, among which anorexia nervosa lies at the extreme end of the spectrum
Progestogen-associated amenorrhea
Depot medroxyprogesterone acetate inhibits the secretion of gonadotrophins and thus suppresses ovulation
After 1 year of use, 80% of women have amenorrhoea or very scanty, infrequent vaginal bleeding
There is partial estrogen deficiency in women who use depot medroxyprogesterone acetate
The progestogen-only pill leads to reversible long-term amenorrhoea in a minority of women, due to complete suppression of ovulation
The levonorgestrel-releasing intra-uterine device commonly results in amenorrhoea after a few months. This is thought to be mainly a local effect, but suppression of ovulation can occur in some women (in some cycles)
ASSESMENT OF ASSESMENT OF SECONDARY AMENORRHEASECONDARY AMENORRHEA
HistoryHistory
A good history can reveal the etiologic A good history can reveal the etiologic diagnosis in up to 85% of cases of diagnosis in up to 85% of cases of
amenorrheaamenorrhea
symptoms of pregnancy Associated symptoms, e.g.
galactorrhoea, hirsutism, hot flushes, dry vagina, symptoms of thyroid disease
Recent change in body weight Recent emotional upsets Previous menstrual and obstetric
history
Previous surgery, e.g. endometrial curettage, oophorectomy
Previous abdominal, pelvic, or cranial radiotherapy
Family history, e.g. of early menopause Drug history, e.g. progestogens,
combined oral contraceptive, chemotherapy
EXAMINATIONEXAMINATION Height and weight: calculate body
mass index if appropriate. Signs of excess androgens, e.g.
hirsutism, acne Signs of virilization, e.g. deep voice,
clitoromegaly in addition to hirsutism, and acne
Signs of thyroid disease
Acanthosis nigricans: this hyperpigmented thickening of the skin folds of the axilla and neck is a sign of profound insulin resistance. It is associated with polycystic ovary syndrome (PCOS) and obesity
Breast examination for galactorrhoea Pelvic examination
Preg.test
TSH ,PROLACTIN, Prog.challenge test
withdrawal bleeding
without withdrawal bleeding
hypoestrogenic compromised outflow tract
++ve.est,progest,challenge test -ve.est,progest
challenge test
FSH>30-40Normal FSH
HSG OR hysteroscopy asherman
FSH low
repeat
POF
hypothalamic-pituitary failure
anovulation
-VE
Complications and prognosis
Osteoporosis: women with amenorrhoea associated with estrogen deficiency are at significant risk of developing osteoporosis. This increased risk persists even if normal menses are resumed. Estrogen deficiency is of particular concern in younger women as a desirable peak bone mass may not be attained
Cardiovascular disease Young women with amenorrhoea associated with estrogen deficiency
may be at increased risk of cardiovascular disease
Women with polycystic ovary syndrome have an increased risk of developing cardiovascular disease, hypertension, and type 2 diabetes [Hopkinson et al, 1998]
Endometrial hyperplasia: women with amenorrhoea but no associated oestrogen deficiency are at increased risk of endometrial hyperplasia and endometrial carcinoma
Infertility: women with amenorrhoea generally do not ovulate
Psychological distress: amenorrhea often causes considerable anxiety, many women have concerns about loss of fertility, loss of femininity, or worry about an unwanted pregnancy. The diagnosis of Turner's syndrome, testicular feminization, or developmental anomaly can be traumatic for both girls and their parents
Complications and prognosis
RECENT MANAGEMENT OF RECENT MANAGEMENT OF AMENORRHEAAMENORRHEA
Ovarian cortical transplantationOvarian cortical transplantationTransplantation of ovarian cortical tissue is Transplantation of ovarian cortical tissue is performed in patients with premature ovarian performed in patients with premature ovarian failure, premature menopause due to sur5gical failure, premature menopause due to sur5gical removal of the ovary, radiotherapy & removal of the ovary, radiotherapy & chemotherapychemotherapythe ovarian cortical grafts transplanted the ovarian cortical grafts transplanted subcutaneously functioned from the 6th subcutaneously functioned from the 6th postoperative month . At the long-term follow-up postoperative month . At the long-term follow-up of the patient, cortical grafts have still been of the patient, cortical grafts have still been functioning. The patient did not have any functioning. The patient did not have any complaint requiring hormonal therapy during that complaint requiring hormonal therapy during that time periodtime period
Ultrasonographic Ultrasonographic appearance of appearance of follicles developed follicles developed from subcutaneous from subcutaneous grafts at the 6th , 9th , grafts at the 6th , 9th , and 18th monthsand 18th months
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